Uropathogenic Escherichia coli (UPEC) is the predominant etiological agent of uncomplicated urinary tract infection (UTI), manifested by inflammation of the urinary bladder, in humans and is a major global public health concern. Molecular pathogenesis of UPEC has been primarily examined using murine models of UTI. Translational research to develop novel therapeutics against this major pathogen, which is becoming increasingly antibiotic resistant, requires a thorough understanding of mechanisms involved in pathogenesis during human UTIs. Total RNA-sequencing (RNAseq) and comparative transcriptional analysis of UTI samples to the UPEC isolates cultured in human urine and laboratory medium were used to identify novel fitness genes that were specifically expressed during human infection. Evidence for UPEC genes involved in ion transport, including copper efflux, nickel and potassium import systems, as key fitness factors in uropathogenesis were generated using an experimental model of UTI. Translational application of this study was investigated by targeting Cus, a bacterial copper efflux system. Copper supplementation in drinking water reduces E. coli colonization in the urinary bladder of mice. Additionally, our results suggest that anaerobic processes in UPEC are involved in promoting fitness during UTI in humans. In summary, RNA-seq was used to establish the transcriptional signature in UPEC during naturally occurring, community acquired UTI in women and multiple novel fitness genes used by UPEC during human infection were identified. The repertoire of UPEC genes involved in UTI presented here will facilitate further translational studies to develop innovative strategies against UTI caused by UPEC.is a global public health concern, especially for women (1). In the United States alone, 7-11 million cases of UTI are reported annually resulting in expenditures of $3.5 billion (2, 3). UPEC is the predominant cause (75-95% of cases) of UTIs in otherwise healthy individuals (1). UTIs caused by UPEC are one of the most common indications for antibiotic prescription and rapid increase in antibiotic resistance in UPEC (4) requires development of next-generation therapeutic agents (5). A targeted approach that selectively diminishes in vivo fitness of pathogens has been proposed as a promising alternative to treatment with conventional antibiotics (6). The molecular mechanisms of UPEC pathogenesis have been extensively investigated, primarily using murine models (7-9). Identification of nextgeneration therapeutics against UPEC, however, requires a thorough knowledge of the fitness and virulence mechanisms involved in the pathogenesis of community-acquired UTIs in humans.Transcriptional profiling, a powerful functional genomic tool, can be used to elucidate host-pathogen interaction during infection (10, 11). UPEC represents a heterogeneous group of bacterial strains (12, 13) and DNA microarrays, based on the sequence of a pyelonephritis strain CFT073, were used in a previous study to determine UPEC genes highly expressed ...

Background Human adenoviruses (HAdVs) are commonly associated with acute respiratory illness. HAdV outbreaks are well documented in congregate military training settings, but less is known about outbreaks on college campuses. During fall 2018 and spring 2019, 5 United States (US) colleges reported increases in HAdV-associated respiratory illness. Investigations were performed to better understand HAdV epidemiology in this setting. Methods A case was defined as a student at one of the 5 colleges, with acute respiratory illness and laboratory-confirmed HAdV infection during October 2018–December 2018 or March–May 2019. Available respiratory specimens were typed by HAdV type-specific real-time polymerase chain reaction assays, and for a subset, whole genome sequencing was performed. We reviewed available medical records and cases were invited to complete a questionnaire, which included questions on symptom presentation, social history, and absenteeism. Results We identified 168 HAdV cases. Median age was 19 (range, 17–22) years and 102 cases (61%) were male. Eleven cases were hospitalized, 10 with pneumonia; 2 cases died. Among questionnaire respondents, 80% (75/94) missed ≥ 1 day of class because of their illness. Among those with a type identified (79%), HAdV types 4 and 7 were equally detected, with frequency of each varying by site. Genome types 4a1 and 7d were identified, respectively, by whole genome sequence analysis. Conclusions HAdV respiratory illness was associated with substantial morbidity and missed class time among young, generally healthy adults on 5 US college campuses. HAdVs should be considered a cause of respiratory illness outbreaks in congregate settings such as college campuses.

Differential pulse polarography and differential pulse anodic stripping voltammetry were used to determine copper, lead, cadmium and zinc complexes of relevance to environmental conditions. The dependency of peak current on pH and alkalinity was interpreted in terms of the variation in the metal species present. Stability constants of copper and lead complexes with carbonate were determined from the magnitude of the shift of peak potential using the method of Lingane. Inclusion of the transfer coefficient, calculated from the peak half-width for electrochemically irreversible systems, was used to determine the stability constant. By using both electroanalytieal techniques, the investigator validates the correctness of his results without needing to rely on prior determinations of the stability constant for verification.

No abstract

Background: The American College of Cardiology/American Heart Association (ACC/AHA) publishes recommendations for cardiac assessment of patients undergoing noncardiac surgery with the intent of promoting evidence-based, efficient preoperative screening and management. We sought to study the impact of guideline implementation for cardiac risk assessment in a general internal medicine preoperative clinic. Methods: The study was an observational cohort study of consecutive patients being evaluated in an outpatient preoperative evaluation clinic before and after implementation of the ACC/AHA guideline. Data was gathered by retrospective abstraction of hospital and clinic charts using standard definitions. 299 patients were reviewed prior to guideline implementation and their care compared to 339 consecutive patients after the guideline was implemented in the clinic. Results: Guideline implementation led to a reduction in exercise stress testing (30.8% before, 16.2% after; p < 0.001) and hospital length of stay (6.5 days before, 5.6 days after; p = 0.055). β-Blocker therapy increased after the intervention (15.7% before; 34.5% after; p < 0.001) and preoperative test appropriateness improved (86% before to 94.1% after; p < 0.001). Conclusions: Implementation of the ACC/AHA guidelines for cardiac risk assessment prior to noncardiac surgery in an internal medicine preoperative assessment clinic led to a more appropriate use of preoperative stress testing and β-blocker therapy while preserving a low rate of cardiac complications.